The purpose of this application is to continue funding for a linkage study of panic disorder that has been in progress for five years. A provisional linkage finding at the alpha-haptoglobin locus was not confirmed in an analysis of 10 new pedigrees. Therefore, the plan for the next 5 years will be to carry out a systematic search of the human genome. Fourteen pedigrees already collected will be supplemented with five new ones each year, cell lines will be cryopreserved, and linkage analyses will be carried out on the DNA using a RFLP map of the human genome. The map will be composed of the most polymorphic markers available from the American Type Culture Collection and the probe sets at Collaborative Research Inc. and the Utah Howard Hughes Institute. Two-point analyses followed by three-point analyses will be used to create exclusion maps for panic disorder for each chromosome. The ultimate aim is to exclude as much of the genome as possible while searching for a susceptibility gene for panic disorder. Provisional evidence of linkage, indicated by a lod score > 1.0, will be further investigated by studying additional probes in the region of interest until linkage can be tentatively confirmed (lod score >3) or excluded (lod score <-2).